Brain metastases

Shaffrey, Mark E.; Mut, Melike; Asher, Anthony L.; Burri, Stuart H.; Chahlavi, Ali; Chang, Susan M.; Farace, Elana; Fiveash, John B.; Hentschel, Stephen J.; Lang, Frederick F.; Lopes, M. Beatriz S.; Markert, James M.; Schiff, David; Siomin, Vitaly; Tatter, Stephen B.; Vogelbaum, Michael A.

doi:10.1067/j.cpsurg.2004.06.001

Cited by 75 publications

(41 citation statements)

References 198 publications

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“…18 -20 Multiple metastases (up to three) can be removed surgically with a risk similar to that of a single lesion, providing similar benefits. 3,16 At present, adjuvant radiotherapy follows surgical resection because this combined approach has been shown in general to prolong median survival significantly, to ϳ12 months depending on the factors noted above. 3,16 There is a growing body of evidence that surgery may be useful in select patients with recurrent brain metastases.…”

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confidence: 99%

“…3,16 At present, adjuvant radiotherapy follows surgical resection because this combined approach has been shown in general to prolong median survival significantly, to ϳ12 months depending on the factors noted above. 3,16 There is a growing body of evidence that surgery may be useful in select patients with recurrent brain metastases. 3,16 Mean survival from diagnosis of a brain metastasis varies between studies but ranges from 2 to 16 months, depending on involvement of the CNS, the extent of the extra-cranial metastatic disease, and the treatment applied.…”

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confidence: 99%

“…3,16 There is a growing body of evidence that surgery may be useful in select patients with recurrent brain metastases. 3,16 Mean survival from diagnosis of a brain metastasis varies between studies but ranges from 2 to 16 months, depending on involvement of the CNS, the extent of the extra-cranial metastatic disease, and the treatment applied. The mean 1-year survival is estimated at ϳ20%.…”

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confidence: 99%

“…16,21 Traditionally, fewer than 2% of patients with breast cancer survive greater than 2 years after the advent of CNS involvement; the inability to control extracranial (systemic) disease has traditionally been the main limiting factor. 1,3,16,21 However, as systemic therapies improve, control of extra-cranial disease may become less influential a predictive factor. This point is strengthened by studies of Her-2-positive patients treated with trastuzumab, a monoclonal antibody against the receptor.…”

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confidence: 99%

“…14,15 Treatment strategies have been reviewed in several recent monographs. 15,16 Many of the randomized studies cited pertain to patients with brain metastases from multiple cancer histologies, including breast cancer. Corticosteroids are used to reduce peri-tumoral edema and provide symptomatic relief.…”

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Breast Cancer Metastasis to the Central Nervous System

Weil

Palmieri

Bronder

et al. 2005

The American Journal of Pathology

389

322

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Clinically symptomatic metastases to the central nervous system (CNS) occur in Natural History of CNS MetastasisOf the nearly 1.3 million people diagnosed with cancer in the United States each year, ϳ100,000 to 170,000 will develop brain metastases, for an annual incidence of ϳ4.1 to 11.1 per 100,000 population (American Cancer Society Cancer Facts and Figures 2005, available at http://www.cancer.org). 1 Large autopsy studies suggest that between 20% and 40% of all patients with metastatic cancer will have brain metastases (http://www.cancer. org). [1][2][3][4] Given their overall greater frequency, lung and breast cancer are by far the most common tumors to present with brain metastases. 2,4 The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10 to 16%. 5 On average, the median latency between the initial diagnosis of breast cancer and the onset of brain metastasis is ϳ2 to 3 years. 1,2 In most cases, breast cancer patients develop brain metastases after metastases have appeared systemically in the lung, liver, and/or bone. 6 For the purposes of this review, central nervous system (CNS) and brain are used interchangeably.Several risk factors for brain metastases have been reported. Young age appears to correlate with elevated risk. 5,7 In a study of 1015 women with metastatic breast cancer, brain metastases occurred in 9% of women with estrogen receptor-negative (ERϪ) primary tumors, compared to 5% of patients with ERϩ primary tumors. 8 Many human breast cancers (25 to 33%) express Her-2, also known as the epidermal growth factor receptor erbB2 or the neu oncogene [Online Mendelian Inheritance in Man (OMIM) accession number 164870; http://www.ncbi. nlm.nih.gov/entrez/dispomim.cgi?id ϭ 164870, accessed 2.25.05]. Amplification or overexpression of Her-2 correlates with a shorter disease-free and overall survival time 9 and also appears to associate with a higher incidence of brain metastases. 10 -12 The metastasis of breast cancer to the CNS, either the brain parenchyma or the leptomeninges, is generally a late feature of metastatic disease. Metastases to the brain parenchyma are thought to be hematogenous in origin. In a retrospective survey of breast cancer patients with brain metastases, 78% had multiple intracerebral metastases, 14% had a solitary intracerebral metastasis, and the remaining 8% had leptomeningeal metastases. 7 Breast cancer is the most common solid tumor to exhibit leptomeningeal colonization. 13 Within the three membranous coverings, or meninges, that surround the brain, leptomeningeal metastases arise on the innermost covering (pia) and the middle membrane (arachnoid) or in the cerebral spinal fluid (CSF)-filled space between the arachnoid and the pia (subarachnoid space). 4 Spread to the leptomeninges may occur via multiple routes including hematogenous, direct extension, transport through

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Breast Cancer Metastasis to the Central Nervous System

Weil

Palmieri

Bronder

et al. 2005

The American Journal of Pathology

389

322

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Pathogenesis and vascular integrity of breast cancer brain metastasis

Wang

Bucana

Schroit

2006

Intl Journal of Cancer

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Dogma dictates that brain metastasis originate from the proliferation of extravasated tumor cells and that the blood-brain barrier (BBB) prevents the delivery of chemotherapeutic drugs to the tumors. The purpose of this study was to clarify the relationship between tumor localization and progression and the involvement of BBB function in a murine model of breast cancer brain metastasis. Green fluorescent protein expressing MDA-MB435 breast cancer cells were injected into the left ventricle of nude mice. At various time points, the entire vasculature was labeled with rhodamine-conjugated albumin. The tumors and vasculature were then imaged by laser-scanning confocal and stereo fluorescence microscopy. About 75% of the cells that reached the brain extravasated and grew perivascularly. Twenty five percent of the cells, however, proliferated within the vasculature and ultimately led to thrombosis-like infarction of the brain parenchyma. The tumorigenic ''embolus'' served as a sustained release source of tumor cells to downstream sites. Continuing intravascular tumor expansion led to disruption of the BBB and to overflow of cells that progressed along the vessels perivascularly to distant sites that regained protection of the BBB. Breast cancer brain metastases involve both extravascular and intravascular growth of tumor cells. These distinct pathways contribute to different pathological phenotypes that generate a heterogeneous BBB that facilitates or inhibits the delivery of chemotherapeutic drugs to the tumor. ' 2006 Wiley-Liss, Inc. Key words: brain metastasis; breast cancerBrain metastases are the most frequently occurring intracranial tumors, outnumbering primary brain tumors by a factor of 10, and represent the major cause of systemic cancer morbidity and mortality.1,2 Their incidence is increasing because of improved cancer therapy for systemic disease.1,3 Most patients die within a few months of diagnosis since systemic therapies are ineffective within the brain. 4 Our knowledge about how brain metastases develop has, for the most part, been extrapolated from observations of tumor growth in other tissues. This has led to the concept that brain metastasis develop after extravasation of metastatic tumor cells into the surrounding tissue 5,6 where they are protected by the blood-brain barrier (BBB) that prevents the delivery of therapeutic agents to the proliferating tumor. 7,8 Because the brain lacks lymphatic drainage, the most common mechanism of brain metastasis is by hematogenous spread through the arterial circulation. By injecting tumor cells into the arterial system to mimic hematogenous spread, we developed a unique breast cancer brain metastasis model that allows us to visualize the development of brain metastasis and monitor BBB function at high resolution. Analysis of breast cancer brain metastases revealed a complex pathogenesis and heterogeneity of BBB integrity. These findings provide a framework for better understanding the clinical presentation of breast cancer and BBB function in brain tumor m...

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Computer‐aided detection of metastatic brain tumors using automated three‐dimensional template matching

Ambrosini

Wang

O’Dell

2009

Magnetic Resonance Imaging

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Purpose: To demonstrate the efficacy of an automated three-dimensional (3D) template matching-based algorithm in detecting brain metastases on conventional MR scans and the potential of our algorithm to be developed into a computer-aided detection tool that will allow radiologists to maintain a high level of detection sensitivity while reducing image reading time. Materials and Methods:Spherical tumor appearance models were created to match the expected geometry of brain metastases while accounting for partial volume effects and offsets due to the cut of MRI sampling planes. A 3D normalized cross-correlation coefficient was calculated between the brain volume and spherical templates of varying radii using a fast frequency domain algorithm to identify likely positions of brain metastases.Results: Algorithm parameters were optimized on training datasets, and then data were collected on 22 patient datasets containing 79 total brain metastases producing a sensitivity of 89.9% with a false positive rate of 0.22 per image slice when restricted to the brain mass.Conclusion: Study results demonstrate that the 3D template matching-based method can be an effective, fast, and accurate approach that could serve as a useful tool for assisting radiologists in providing earlier and more definitive diagnoses of metastases within the brain.

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Brain metastases

Cited by 75 publications

References 198 publications

Breast Cancer Metastasis to the Central Nervous System

Breast Cancer Metastasis to the Central Nervous System

Pathogenesis and vascular integrity of breast cancer brain metastasis

Computer‐aided detection of metastatic brain tumors using automated three‐dimensional template matching

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